Emerging Roles of the Gut Microbiome in Musculoskeletal Injury and Repair.

Abstract

Over the past decade, significant attention has been directed toward understanding the role of the gut microbiome in health and disease. The gut microbiota, comprising a complex and diverse community of microorganisms, has been linked to numerous conditions, including metabolic disorders, gastrointestinal diseases, and inflammatory or autoimmune conditions. Recently, a growing body of evidence has revealed a compelling relationship between gut microbiota composition and musculoskeletal injury recovery, highlighting its potential as a novel therapeutic target. Musculoskeletal injuries, including fractures, post-traumatic osteoarthritis, and tendon or ligament injuries, commonly lead to changes in the community structure of the gut microbiota, intestinal permeability, and systemic inflammation, processes known to negatively influence tissue repair. Preclinical studies demonstrate that microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, effectively restore gut barrier integrity, modulate inflammation, and normalize gut-derived metabolite profiles. Despite these promising findings, critical gaps remain in translating these effects into clinical practice, particularly regarding the mechanisms linking specific microbiota changes to improved musculoskeletal healing outcomes. Future research incorporating rigorous clinical trials, multi-omics analyses, and advanced predictive tools, including artificial intelligence and microbiome-informed digital twins, is urgently needed to fully harness the therapeutic potential of microbiome-based interventions in musculoskeletal injury recovery. This narrative review provides insights into our evolving understanding of the relationship between the gut microbiota and musculoskeletal injury and explores the potential of gut microbiota-targeted therapies for improved healing outcomes.